Efficacy of Novel Syk-Kinase Inhibitors MT-SYK-03 and MT-SYK-322 in Cellular Models of Autoimmunity and Cancer

2012 ◽  
Vol 22 (6) ◽  
pp. 287-289 ◽  
Author(s):  
Tatiana V. Rakitina ◽  
Alexey A. Zeifman ◽  
Ilya Yu. Titov ◽  
Igor V. Svitanko ◽  
Aleksey V. Lipkin ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Cellular Models ◽  
Syk Kinase

Rational design and synthesis of novel Syk-kinase inhibitors

2012 ◽  
Vol 22 (2) ◽  
pp. 73-74 ◽  
Author(s):  
Alexey A. Zeifman ◽  
Ilya Yu. Titov ◽  
Igor V. Svitanko ◽  
Tatiana V. Rakitina ◽  
Aleksey V. Lipkin ◽  
...  
Keyword(s):  
Rational Design ◽  
Kinase Inhibitors ◽  
Design And Synthesis ◽  
Syk Kinase

scholarly journals Syk Kinase Inhibitors Synergize with Artemisinins by Enhancing Oxidative Stress in Plasmodium falciparum-Parasitized Erythrocytes

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 753 ◽  
Author(s):  
Ioannis Tsamesidis ◽  
Karine Reybier ◽  
Giuseppe Marchetti ◽  
Maria Carmina Pau ◽  
Patrizia Virdis ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Plasmodium Falciparum ◽  
Kinase Inhibitors ◽  
Active Form ◽  
Plasmodium Falciparum Malaria ◽  
Reactive Iron ◽  
Syk Kinase ◽  
Redox Active ◽  
Virtuous Cycle ◽  
Greater Mekong Subregion

Although artemisinin-based combination therapies (ACTs) treat Plasmodium falciparum malaria effectively throughout most of the world, the recent expansion of ACT-resistant strains in some countries of the Greater Mekong Subregion (GMS) further increased the interest in improving the effectiveness of treatment and counteracting resistance. Recognizing that (1) partially denatured hemoglobin containing reactive iron (hemichromes) is generated in parasitized red blood cells (pRBC) by oxidative stress, (2) redox-active hemichromes have the potential to enhance oxidative stress triggered by the parasite and the activation of artemisinin to its pharmaceutically active form, and (3) Syk kinase inhibitors block the release of membrane microparticles containing hemichromes, we hypothesized that increasing hemichrome content in parasitized erythrocytes through the inhibition of Syk kinase might trigger a virtuous cycle involving the activation of artemisinin, the enhancement of oxidative stress elicited by activated artemisinin, and a further increase in hemichrome production. We demonstrate here that artemisinin indeed augments oxidative stress within parasitized RBCs and that Syk kinase inhibitors further increase iron-dependent oxidative stress, synergizing with artemisinin in killing the parasite. We then demonstrate that Syk kinase inhibitors achieve this oxidative enhancement by preventing parasite-induced release of erythrocyte-derived microparticles containing redox-active hemichromes. We also observe that Syk kinase inhibitors do not promote oxidative toxicity to healthy RBCs as they do not produce appreciable amounts of hemichromes. Since some Syk kinase inhibitors can be taken daily with minimal side effects, we propose that Syk kinase inhibitors could evidently contribute to the potentiation of ACTs.

scholarly journals Targeting eIF4F translation complex sensitizes B-ALL cells to tyrosine kinase inhibition

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thanh-Trang Vo ◽  
Lee-or Herzog ◽  
Roberta Buono ◽  
Jong-Hoon Scott Lee ◽  
Sharmila Mallya ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
B Cell ◽  
Kinase Inhibitors ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Selective Inhibition ◽  
Initiation Factor ◽  
Leukemia Cells ◽  
Cellular Models ◽  
Eif4f Complex

AbstractThe mechanistic target of rapamycin (mTOR) is a kinase whose activation is associated with poor prognosis in pre-B cell acute lymphoblastic leukemia (B-ALL). These and other findings have prompted diverse strategies for targeting mTOR signaling in B-ALL and other B-cell malignancies. In cellular models of Philadelphia Chromosome-positive (Ph+) B-ALL, mTOR kinase inhibitors (TOR-KIs) that inhibit both mTOR-complex-1 (mTORC1) and mTOR-complex-2 (mTORC2) enhance the cytotoxicity of tyrosine kinase inhibitors (TKIs) such as dasatinib. However, TOR-KIs have not shown substantial efficacy at tolerated doses in blood cancer clinical trials. Selective inhibition of mTORC1 or downstream effectors provides alternative strategies that may improve selectivity towards leukemia cells. Of particular interest is the eukaryotic initiation factor 4F (eIF4F) complex that mediates cap-dependent translation. Here we use novel chemical and genetic approaches to show that selective targeting of either mTORC1 kinase activity or components of the eIF4F complex sensitizes murine BCR-ABL-dependent pre-B leukemia cells to dasatinib. SBI-756, a small molecule inhibitor of eIF4F assembly, sensitizes human Ph+ and Ph-like B-ALL cells to dasatinib cytotoxicity without affecting survival of T lymphocytes or natural killer cells. These findings support the further evaluation of eIF4F-targeted molecules in combination therapies with TKIs in B-ALL and other blood cancers.

CHAPTER 7. Syk Kinase Inhibitors

2012 ◽  
pp. 181-210
Author(s):  
Neelu Kaila ◽  
MARK S. RYAN ◽  
Atli Thorarensen ◽  
EDDINE SAIAH
Keyword(s):  
Kinase Inhibitors ◽  
Syk Kinase

Syk kinase inhibitors in allergic diseases

2009 ◽  
Vol 22 (3) ◽  
pp. 146 ◽  
Author(s):  
J. Denyer ◽  
V. Patel
Keyword(s):  
Kinase Inhibitors ◽  
Allergic Diseases ◽  
Syk Kinase

Pyrazine-based Syk kinase inhibitors

2012 ◽  
Vol 22 (8) ◽  
pp. 2784-2788 ◽  
Author(s):  
Pilar Forns ◽  
Cristina Esteve ◽  
Lorena Taboada ◽  
Juan Antonio Alonso ◽  
Adelina Orellana ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Syk Kinase
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